Presentation on theme: "Acute Liver Failure. Topics Definitions of failure and classification Aetiology- Acute versus acute on chronic Basic diagnostic workup Liver biopsy in."— Presentation transcript:
Acute Liver Failure
Topics Definitions of failure and classification Aetiology- Acute versus acute on chronic Basic diagnostic workup Liver biopsy in the context ACLF-Ethical dilemma- HDU admission Treatment of complication Hepatic encephalopathy Renal failure GI bleed Infection Coagulopathy Aetiology specific treatment Organ support Liaison with Transplant centre
The mortality rate for acute liver failure ranges between 56% and 80%
Abnormal LFT is NOT ALF Dear Doctor Patients bilirubin is 600 and has liver failure- kindly urgently see Family was told transplant may be necessary
Formal diagnosis of acute liver failure An increase in PT by 4-6 seconds (INR>1.5) And the development of hepatic encephalopathy (HE). In a patient without pre-existing cirrhosis and with an illness of less than six months duration.
UK incidence of cirrhosis 17 per 100,000 Prevalence of cirrhosis is 76 per 100,000 ALF incidence is 1-6 per million per year
aCLF This entity is quite common- background of cirrhosis. Innocent precipitating event culminates in MOF Events Toxins (alcohol!) Vascular (hypotension- GI bleed, dehydration, Portal vein thrombosis) Infection (SBP) HCC
ACLF-Ethical dilemma- HDU admission
For patients with aCLF Young age First presentation Reversible pathology- sepsis, GI bleeding or severe hepatitis A trip to ITU is a life changing experience to some alcoholics
Few definitions Hyperacute- <7days Acute - >7days <21days Subacute- >21days <6months FHF- not used
Diagnostics: Good history- difficult if HE
Initial Laboratory Analysis- general Prothrombin Time/INR Blood Chemistry Sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphate, AST, ALT, alkaline phosphatase, GGT, total bilirubin, albumin, Creatinine, urea Glucose Arterial blood gas Arterial lactate Full blood count Blood type and screen Ammonia (arterial if possible) HIV status Amylase and lipase
Phase I – 0-24h Anorexia, nausea and vomiting, malaise LFT derrangement at 12h Phase II – 18-72h RUQ pain LFT derrangment Phase III – 72-96h Centrilobar necrosis Liver failure Phase IV – 4d-3wk Recovery, transplant or death No chronic state
When to pick up the phone D2- pH <7.3 INR>3 Cr >200 Hypoglycaemia D3- HE Cr>200 INR >4.5 D4- Any rise in INR Cr >250 HE
Definition: HRS ARF in a patient CLD, severe alcoholic hepatitis or ALF from any cause End-stage of reduction in renal perfusion induced by increasingly severe hepatic injury.
1.Sinusoidal portal hypertension, in the presence of severe hepatic decompensation 2.Leads to splanchnic and systemic vasodilatation-role of NO 3.Decreased effective arterial blood volume 4.Activation of RAS, and vasopressin aimed at restoring arterial filling pressure. 5.Renal vasoconstriction increases counterbalanced by the intrarenal prostaglandins. 6.When this balance is lost renal hemodynamics worsens, and hepatorenal syndrome develops
HRS Major criteria Chronic or acute hepatic disease and liver failure with portal hypertension Serum creatinine level >133 micromoles/L Absence of shock, ongoing bacterial infection, recent use of nephrotoxic drugs, excessive fluid or blood loss No sustained improvement in renal function after volume expansion with 1.5 L isotonic saline solution No Proteinuria (Protein<500 mg/day) and no ultrasonographic evidence of renal tract or parenchymal disease Minor criteria Urine volume <500 mL/day Urine sodium <10 mEq/L Urine osmolality greater than plasma osmolality Urine red blood cell count <50 per high-power field Serum sodium <130 mEq/L
Classification of HRS Type I is defined by a rise in creatinine level to over 221 micromoles/L in less than 2 weeks Median survival of 2 weeks Type II is defined as less severe renal insufficiency; it is principally characterized by ascites that is resistant to diuretics. Median survival of 3-6 months.
Vasoactive Medical treatment Terlipressin bolus(0.5mg/4h)-increase every 3 days if no response to 1-2mg/4h Given until creatinine normalizes or for 15 days Albumin 1g/kg on day1( one bag of HAS contains 20grams) 20-60g/d thereafter
Step by step guide : Normal renal us Normal urine dipsix – no RBC cast No nephrotoxic drugs Fluid challenge Spot Na and serum Na Serum and urine osmolality Urine output PRERENA L HRSATN Spot Na<10 >30 Urine sediment Nil Positive Fluid challenge RespondsNil
The stages of HE- West Haven criteria: Stage 0. Lack of detectable changes in personality or behaviour. Asterixis absent. Stage 1. Trivial lack of awareness. Shortened attention span. Impaired addition or subtraction. Hypersomnia, insomnia, or inversion of sleep pattern. Euphoria or depression. Asterixis can be detected. Stage 2. Lethargy or apathy. Disorientation. Inappropriate behaviour. Slurred speech. Obvious asterixis. Stage 3. Gross disorientation. Bizarre behaviour. Semistupor to stupor. Asterixis generally absent. Stage 4. Coma.
HE- Four compatible theories Cerebral vasomotor dysfunction Oedema secondary to ammonia toxicity Inflammation due to SIRS putative benzodiazepine-like molecules
The pathophysiology of HE A large body of work points at ammonia as a key factor in the pathogenesis of HE. Portal ammonia is derived from both the urease activity of colonic bacteria and the deamidation of glutamine in the small bowel. The intact liver clears almost all of the portal vein ammonia, converting it into glutamine and preventing entry into the systemic circulation. Ammonia- astrocyte swelling in brain
Patients with grade II HE should be managed in a HDU environment. Grades III and IV HE requires definitive airway protection and appropriate monitoring. Grade IV HE is strongly associated with elevated levels of serum ammonia, a high incidence of raised intracranial pressure and the development of uncal herniation.
In acute and chronic liver disease, increased arterial levels of ammonia are commonly seen. However, correlation of blood levels with mental state in cirrhosis is inaccurate.
Lactulose is a first-line pharmacological treatment of HE. Lactulose – reaches colon, where bacteria will metabolize the lactulose to acetic acid and lactic acid. This lowers the colonic pH formation of the non-absorbable NH4+ from NH3, Other effects like catharsis also contribute to the clinical effectiveness of lactulose.
Lactulose For acute encephalopathy, lactulose (ingested or via nasogastric tube), 45 ml p.o., Is followed by dosing every hour until evacuation occurs. Target -three soft bowel movements per day If response to disachharide is poor- add antibiotic (metronidazole or rifaximine after 48Hrs) to reduce enteric bacterial mass.
If patient is refusing oral lactulose prescribe phosphate enemas TDS! An excessively sweet taste, flatulence, and abdominal cramping are the most frequent subjective complaints with this drug.
The coagulopathy of liver disease Failure to produce clotting factors II, V, VII and IX Failure of the diseased liver to clear activated clotting factors. Degree of hypersplenism and thrombocytopaenia often adds to the coagulopathy, especially if disseminated intravascular coagulation (dic) also co- exists. The degree of coagulopathy is a measure of severity of liver disease and of patient prognosis. Routine correction of coaguloapthy is therefore NOT indicated unless active bleeding or planned interventions require it
Sepsis Infection may be the initiating event of liver failure, Intercurrent sepsis is also a common problem. Impaired immune function, in part secondary to reduced complement factor production and Impaired neutrophil, leukocyte and monocyte function, can result in delayed presentation of clinical signs of infection. The interventions required for diagnosis and management of liver disease also increase patient vulnerability to invasive infection.
Role of prophylactic antibiotic Only patients who have an episode of gastrointestinal bleeding or an episode of spontaneous bacterial peritonitis (SBP) have been shown to have a significant outcome benefit from prophylactic antibiotics.
In presence of sepsis Choice of antibiotic should be guided by local microbiological surveillance. The high incidence of mycoses - low threshold for antifungal. Regular microbiological surveillance
Role of NAC Efficacy of NAC is well established in PCM induced ALF Non PCM ALF – role of NAC is controversial 175 patients of non PCM ALF received NAC Transplant free survival at 3 weeks was 52% in NAC group compared to 30% in placebo arm ( only with coma grade of 1-2) United States ALF study group- overall was 70% vs 66%
Extracorporeal Liver Assist Device (ELAD) Hepatocyte bioreactor- hepatoma cells cultivated on the exterior surface of semipermeable hollow fibres MARS (molecular adsorbent recirculating system)
ELAD Both reduce the level of bilirubin, bile salt ammonia etc However no of patients dying or requiring liver transplant did not improve Devices remain experimental and large-scale phase two and three trials are awaited
Summary The mortality rate for acute liver failure ranges between 56% and 80% The main role of intensive care therapy is multi-organ support The commonest cause of acute liver failure in the western world is paracetamol toxicity Hepatic encephalopathy is no longer the main cause of death but its detection and management requires sophisticated cardiovascular and cerebral monitoring Hepatorenal failure is due to the complex interplay between splanchnic, renal and systemic circulatory responses to liver failure. Terlipressin has been shown to be of use in its treatment Novel hepatic replacement therapies are under development but definitive studies as to their efficacy are, as yet, unpublished.